The long-term goal of the proposed research is to increase understanding of certain aspects of blood coagulation and platelets, and their relationship to hemorrhagic and thrombotic disorders. Studies are designed to increase understanding of the basic mechanisms involved, and to relate this information to clinical disorders of hemostasis. Of particular interest are the mechanisms of control of platelet and fibrinogen production; the effects of bacterial endotoxin on blood coagulation and platelets, and their relationship to disseminated intravascular coagulopathy; the physiologic effects of ancrod (Arvin), a proteolytic enzyme obtained from the venom of the Malayan pit viper, Agkistrodon rhodostoma, and application of the action of this drug to produce therapeutic defibrination and assist in the treatment of thrombotic disease. Additional understanding of blood coagulation and platelet function in humans will be sought through comparatve studies on invertebrate coagulation, especially in Limulus polyphemus, the horseshoe crab. Lysates of Limulus amebocytes will be used as a sensitive in vitro assay for bacterial endotoxin in human diseases and in animal models, in order to determine the role of endotoxin in certain disorders of blood coagulation will also be investigated including: heparininduced thrombocytomenia, treatment of thromboemboli with tissue culture urokinase, disseminated intravascular coagulopathy, and von Willebrand's disease and the hemophilias.